Synthesis of new acyl, furoyl, and benzoylthiocarbamates as polydentate systems. Structural study of isopropyl N-(2-furoyl)thiocarbamate

Article abstract of DOI:10.1016/j.tet.2005.04.018

Synthesis of new acylthiocarbamates has been carried out. To establish the preferential conformation and to explain the behaviour chemically, the structure of isopropyl N-(2-furoyl)thiocarbamate 3m has been determined by single-crystal X-ray analysis. The most stable conformation E,Z′ established by X-ray analysis was corroborated by semiempirical theoretical calculations.

Full text of DOI:10.1016/j.tet.2005.04.018

Tetrahedron 61 (2005) 5812–5817
Synthesis of new acyl, furoyl, and benzoylthiocarbamates
as polydentate systems. Structural study
of isopropyl N-(2-furoyl)thiocarbamate
a
Ana M. Plutın, Margarita Suarez, Estael Ochoa, Teresita Machado, Raul Mocelo,
a,
a
a
a
*
´
´
Jose M. Concellon and Humberto Rodrıguez-Solla
´
b,
b
*
´
´
´
a
´ ´ ´
Laboratorio de Sıntesis Organica, Facultad de Quımica, Universidad de La Habana, 10400 La Habana, Cuba
´
b
´ ´ ´ ´
Departamento de Quımica Organica e Inorganica, Facultad de Quımica, Universidad de Oviedo, Julian Claverıa, 8, 33071 Oviedo, Spain
´
Received 11 February 2005; revised 29 March 2005; accepted 11 April 2005
Available online 10 May 2005
Abstract—Synthesis of new acylthiocarbamates has been carried out. To establish the preferential conformation and to explain the
behaviour chemically, the structure of isopropyl N-(2-furoyl)thiocarbamate 3m has been determined by single-crystal X-ray analysis. The
most stable conformation E,Z0 established by X-ray analysis was corroborated by semiempirical theoretical calculations.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
Some organic sulfur compounds such as thiocarbamates
show important biological activity.1 Most notably, acylthio-
carbamates are used as biosensors,2 elastase inhibitors,3 and
they can exhibit antineoplasic and antiinflammatory or
antiarthritic1 effects. Also molecular modelling studies of
related acylthiocarbamates has been previously carried out
due to they are potent non-nucleoside HIV-1 reverse
transcriptase inhibitors.4
Figure 1.
carbamates.7 X-ray and semiempirical calculations would
complete the structural determination of acylthiocarbamates
in the literature and would be useful to understand the
behaviour of these compounds versus electrophiles.
In addition, acylthiocarbamates have also been employed as
starting compounds to obtain different heterocyclic com-
pounds such as aminothiazoles, thietanes, aminotetrazoles,
thiadiazoles, or thiadiazolines.5 Some of these compounds
are important since they are intermediates en route to variety
of drugs.6
Previously, we reported the synthesis of 1-benzoyl-3-
alkylureas, using microwaves, through transamidation
reactions,9 and the alkylation of benzoyl and furoylthioureas
as polydentate systems.10 Here, we describe the synthesis of
new acyl, furoyl and benzoylthiocarbamates and we have
determined the structure of isopropyl N-(2-furoyl)thio-
carbamate 3m by single-crystal X-ray analysis. We have
also confirmed that E,Z0 is the most stable conformation
using the X-ray data and semiempirical theoretical
calculations.
Thiocarbamates can react with weak bases, such as sodium
or potassium carbonate, generating the corresponding anion,
which can be represented through four plausible confor-
mations as shown in Figure 1.7 Molecular mechanics
calculations onto N-acylthiocarbamate predict that E,Z0 is
the most stable conformation.8 Likewise, Schroeder et al.
established, by using nuclear magnetic resonance, that E,Z0
was the most stable conformation in N-benzoyl-O-alkylthio-
Keywords: Thiocarbamates; Acylthiocarbamates; Structural studies; Semi-
empirical methods.
*
Corresponding authors. Tel.: C34 985103457; fax: C34 985103446
(J.M.C.); e-mail: jmcg@fq.uniovi.es
Scheme 1.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.04.018

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A. M. Plutın et al. / Tetrahedron 61 (2005) 5812–5817
5813
Table 1. Synthesis of compounds 3
Entry
3
R1
R2
Yield (%)
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
t-Bu
t-Bu
t-Bu
Ph
Ph
Ph
Ph
Me
Et
i-Pr
n-C5H11
s-C5H11
i-C5H11
n-C18H37
Bn
i-Pr
i-Pr
Me
Et
i-Pr
Bn
Me
Et
68
67
70
74
78
76
72
81
71
74
72
74
73
78
78
78
78
Ph
9
pNO2–C6H4
pF–C6H4
Furyl
10
11
12
13
14
15
16
17
Furyl
Furyl
Furyl
2-(2-Furyl)vinyl
2-(2-Furyl)vinyl
2-(2-Furyl)vinyl
i-Pr
2. Results and discussion
smaller aliphatic chain were used, products 3 were obtained
in lower yields due to the generation of 4. This fact could be
explained assuming steric effects, as stated before.
The thiocarbamates were prepared by using acid chlorides 1
and ammonium thiocyanate in acetone. The intermediate
isothiocyanate 2 reacts in situ with the corresponding
alcohol affording the thiocarbamate 3 (Scheme 1 and
Table 1).
To study the structure of acylthiocarbamates, isopropyl
N-(2-furoyl)thiocarbamate (3m) was used as compound
model. Thus, X-ray diffraction and semiempirical methods
were employed to reveal the most stable conformation of
3m (Fig. 1).
Although there are two electrophilic carbon centres in 2, the
major product obtained is 3, a consequence of the alcohol
addition to the isocyanate electrophilic carbon (Scheme 2).
X-ray analysis of 3m shows that fragments S1]C6–N1–
C5]O2 are in a nearly planar alignment with a torsion
angle S1–C6–N1–C5ZK177(2)8 and C6–N1–C5–O2Z
K3(4)8 (Fig. 2).
Scheme 2.
AM1, and PM3 semiempirical calculations predict a slightly
negative charge value (K0.035, and K0.00075, respect-
ively) on the carbon in the thiocarbamoyl group in products
2 (R1ZPh). However, steric effects on the carbonyl group
lead to products 3 in high yields instead of compounds 4.
In the case of net charges values on C]O, AM1 and PM3
methods predict 0.418 and 0.408, respectively.
Figure 2. X-ray structure of compound 3m showing the numbering scheme.
Asymmetry in angles C3–C4–C5 and O1–C4–C5 [131.8(5)
and 118.9(4)8, respectively] could be due to the repulsion in
the C3–H3/O2 system [C3$O2Z3.006(6), H3/O2Z
˚
2.96 A] and the attraction in the NH/O1 system
Synthesis of acylthiocarbamates seems to be general: a
variety of aliphatic and aromatic alcohols were shown to be
applicable. In general, slightly higher yields were obtained
from aromatic, or conjugated alcohols 3d–q in comparison
to aliphatic alcohols 3a–c. This result could be explained
taking into account that aliphatic acylisothiocyanates are
more reactive than conjugated or aromatic equivalents: the
decomposition of these products afforded the corresponding
acid. Scheme 2 illustrates the two possible mechanisms of
the reaction of alcohols with isothiocyanates 2. When the
aliphatic chain in alcohols is branched, better yields were
observed in the reaction to afford 3. When alcohols with
˚
˚
[N/O1Z2.654(6) A, H/O1Z2.19 A]. Taking into
account that distances in C5–N1 and C6–N1 are 1.389(6)
˚
and 1.377(6) A, respectively, it is possible to assume an
electronic delocalization in that part of the molecule.
˚
In addition, C6–O3 bond distance [1.300(7) A] indicates a
partial double bond and a p-type conjugation in the whole
system, this observation is in agreement with the previously
reported results.7
In order to predict the minimum energy conformation, and
relative stability of the possible conformers for 3m, the

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A. M. Plutın et al. / Tetrahedron 61 (2005) 5812–5817
5814
Figure 3. Heat of formation versus torsion angle O2–C5–N1–C6 (S1–C6–N1–C5Z180 and 08, respectively) for compound 3m.
semiempirical PM3 method was used. The strategy was to
study the heat of formation against the torsion angle related
to the interconversion of these conformations.11 Figure 3
represents the variation of the torsion angle that corresponds
to the interconversion E,E0 E,Z0 and Z,E0 Z,Z0, respectively.
In the second case (Fig. 3b), the torsion angle O2–C5–N1–
C6 was again rotated every 58 from K1808 (Z,E0) to 1808
(Z,E0) passing through 08 (Z,Z0), and the torsion angle
S1–C6–N1–C5 was fixed at 08.
In this sense, Figure 3 shows that the four conformers are
consistent with the minimum energy in the curve and are
close in energy (heat of formation around K50 kcal/mol).
A complete optimisation onto the geometry corresponding
to the energetic minimum was carried out and
In the first case (Fig. 3a), the torsion angle O2–C5–N1–C6
was rotated every 58 from K1808 (E,E0) to 1808 (E,E0)
passing through 08 (E,Z0), the torsion angle S1–C6–N1–C5
being fixed at 1808.
˚
Table 2. Bond distances, valence angles, and torsion angles for compound 3m (the numbering scheme is shown in Figure 2). Bond distances are given in A and
angles in degrees (standard deviations in parenthesis)
3m
PM3
X-ray
3m
PM3
X-ray
Bond distances
C1–C2
C1–O1
C2–C3
C3–C4
C4–O1
C4–C5
C5–O2
C5–N1
1.375
1.370
1.437
1.379
1.393
1.476
1.215
1.445
1.317(9)
1.382(6)
1.411(8)
1.343(7)
1.362(7)
1.466(7)
1.198(6)
1.389(6)
C6–O3
C6–N1
C6–S1
C7–C9
C7–O3
C7–C8
N1–H1
1.344
1.404
1.654
1.523
1.449
1.523
1.001
1.300(7)
1.377(6)
1.635(6)
1.46(3)
1.486(8)
1.50(4)
0.8600
Valence angles
C2–C1–O1
C1–C2–C3
C4–C3–C2
C3–C4–O1
C3–C4–C5
O1–C4–C5
O2–C5–N1
O2–C5–C4
N1–C5–C4
O3–C6–N1
110.8
111.1(6)
106.1(6)
107.5(5)
109.6(5)
131.9(5)
118.3(5)
124.3(5)
122.4(5)
113.0(5)
111.5(5)
O3–C6–S1
N1–C6–S1
C9–C7–O3
C9–C7–C8
O3–C7–C8
C4–O1–C1
C6–O3–C7
C6–N1–C5
C6–N1–H1
C5–N1–H1
131.5
127.8(5)
119.8(4)
108.3(15)
112.3(7)
103.0(2)
105.3(5)
120.3(4)
131.7(4)
114.2
106.4
106.4
109.8
129.6
120.6
121.0
122.4
116.6
107.5
120.9
107.1
111.5
107.1
106.6
118.3
129.9
112.8
117.1
114.2
Torsion angles
O1–C1–C2–C3
C1–C2–C3–C4
C2–C3–C4–O1
C2–C3–C4–C5
C3–C4–C5–O2
O1–C4–C5–O2
C3–C4–C5–N1
O1–C4–C5–N1
C3–C4–O1–C1
C5–C4–O1–C1
0.0
0.1
K0.2
K179.3
8.8
K170.2
K170.1
0.8
0.2
179.4
6(4)
K3(3)
K1(3)
K177(3)
4(5)
K170(3)
178(3)
3(3)
C2–C1–O1–C4
N1–C6–O3–C7
S1–C6–O3–C7
C9–C7–O3–C6
C8–C7–O3–C6
O3–C6–N1–C5
S1–C6–N1–C5
O2–C5–N1–C6
C4–C5–N1–C6
K0.1
180.0
1.0
120.0
K120.3
7.7
K173.3
7.2
K173.7
K7(4)
K173(2)
K4(5)
129(2)
K112(3)
K7(4)
K177(2)
K3(4)
K177(3)
5(4)
K179(2)

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A. M. Plutın et al. / Tetrahedron 61 (2005) 5812–5817
5815
E,E0ZK51.3 kcal/mol; E,Z0ZK54.4 kcal/mol; Z,E0Z
K51.2 kcal/mol and Z,Z0ZK51.9 kcal/mol heats of forma-
tion were found. This lead us to state that E,Z0 conformation
is the most stable. This result is in agreement with the
experimental data from X-ray analysis, in which the torsion
angles are S1–C6–N1–C5ZK177(2) and O2–C5–N1–C6Z
K3(4)8. This also explains that the carbonyl and thiocarbo-
nyl 0groups are in opposite positions, the molecule being in a
E,Z conformation (Fig. 2).
3 and 8 h. The progress of the reaction was monitored by
TLC (using benzene/methanol (9/1) as eluent). When the
reaction was completed the product was poured into 100 mL
of cold water. The solid acylthiocarbamates were filtered
out. Purification of compounds 3 were performed by
recrystallization using acetone–H2O as solvent.
4.2.1. Methyl N-pivaloylthiocarbamate 3a. 68% Yield;
mp 69–70 8C; nmax/cmK1 3282 (NH), 2966 (C–H), 1714
(C]O), 1525 (NH), 1278 (C]S); dH (d6-DMSO,
250 MHz), 8.72 (br s, 1H), 4.09 (s, 3H), 1.22 (s, 9H); dC
(d6-DMSO, 62 MHz), 190.7 (CS), 173.6 (CO), 59.5
(OCH3), 40.3 (C), 27.1 (CH3).
Table 2 shows selected data of bond distances, bond angles
and torsion angles, obtained from X-ray diffraction studies
and values from the semiempirical method PM3 for 3m.
Both methods showed a satisfactory correspondence. These
results confirmed that the semiempirical method PM3,
reports a reliable geometry for the propose systems.
4.2.2. Ethyl N-pivaloylthiocarbamate 3b. 67% Yield; mp
90–92 8C; nmax/cmK1 3314 (NH), 2983 (CH), 1709 (C]O),
1518 (NH), 1272 (C]S); dH (d6-DMSO, 250 MHz), 8.67
(br s, 1H), 4.58 (q, JZ6 Hz, 2H), 1.41 (t, JZ6 Hz, 3H), 1.22
(s, 9H); dC (d6-DMSO, 62 MHz), 189.9 (CS), 173.5 (CO),
69.5 (CH2), 40.3 (C), 27.1 [(CH3)3C], 13.8 (CH3).
3. Conclusion
In conclusion, a synthesis of new acythiocarbamates has
been carried out. X-ray analysis and semiempirical
theoretical calculations, established that the most stable
conformation in acylthiocarbamates as E,Z0.
4.2.3. Isopropyl N-pivaloylthiocarbamate 3c. 70% Yield;
mp 76–78 8C; nmax/cmK1 3207 (NH), 2980 (CH), 1720
(C]O), 1523 (NH), 1290 (C]S); dH (d6-DMSO,
250 MHz), 8.57 (br s, 1H), 5.54 (hept, JZ6.5 Hz, 1H),
1.42 (d, JZ6.5 Hz, 6H), 1.24 (s, 9H); dC (d6-DMSO,
62 MHz), 189.1 (CS), 173.3 (CO), 77.6 [CH(CH3)2], 40.2
[C(CH3)3], 27.1 [C(CH3)3], 21.2 (CH3).
4. Experimental
4.1. General experimental
4.2.4. n-Pentyl N-benzoylthiocarbamate 3d. 74% Yield;
mp 69–71 8C; nmax/cmK1 3208 (NH), 3063 (CH), 2956
(CH), 1696 (C]O), 1601 (C]C), 1300 (C]S), 1462
(CH3); dH (CDCl3, 250 MHz), 9.32 (br s, 1H), 7.90–7.40 (m,
5H), 4.60 (t, JZ6.2 Hz, 2H), 1.85–1.75 (m, 2H), 1.40–1.35
(m, 4H), 0.95 (t, JZ6.2 Hz, 3H); dC (CDCl3, 62 MHz) 189.7
(CS), 162.8 (CO), 133.1 (C8), 133.0 (C5), 128.9 (C6 and
C10), 127.8 (C7 and C9), 73.7 (OCH2), 27.9 (CH2)2CH2O,
22.3 (CH2CH3), 13.9 (CH3); MS (EI): m/z (%), 251 (5), 181
(25), 121 (18), 105 (100), 77 (72), 51 (34); elemental
analysis calcd (%) for C13H17NO2S: C, 62.12; H, 6.82; N,
5.57. Found: C, 62.04; H, 6.96; N, 5.41.
Reactions which required an inert atmosphere were
conducted under dry nitrogen, and the glassware was oven
dried (120 8C). All reagents were purchased from Aldrich or
Merck and were used without further purification. Silica gel
for flash chromatography was purchased from Scharlau or
Merck (200–450 mesh), and compounds were visualized
(UV light, 254 nm) on analytical thin layer chromatograms
(TLC) and using benzene/methanol (9/1) as eluent. 1H NMR
spectra were recorded on a Bruker AC spectrometer at
250 MHz. 13C NMR spectra and DEPT experiments were
determined at 62 MHz. Chemical shifts are given in ppm
relative to tetramethylsilane (TMS), which was used as an
internal standard, and coupling constants J are reported
in Hz. Melting points (mp) were determined on an
Electrothermal C14500 apparatus and are uncorrected. IR
spectra (nmax/cmK1) were recorded on a Bruker IRS48
instrument using KBr disc. MS (electronic impact) spectra
were measured at 70 eV. Only the most important IR
absorptions (cmK1) and the molecular ions and/or base
peaks in MS are given. Microanalyses were performed by
4.2.5. 2-Pentyl N-benzoylthiocarbamate 3e. 78% Yield;
mp 64–65 8C; dH (CDCl3, 250 MHz), 9.28 (br s, 1H), 7.90–
7.40 (m, 5H), 5.60–5.55 (m, 1H), 1.80–1.60 (m, 2H), 1.45–
1.40 (m, 4H), 0.90–0.85 (m, 3H); dC (CDCl3, 62 MHz),
189.6 (CS), 162.8 (CO), 133.1 (C8), 133.0 (C5), 128.9
(C6 and C10), 127.8 (C7 and C9), 81.1 (OCH2), 37.5
(OCH2CH2), 19.1 [CH(CH3)2], 18.4 (CH3), 13.9 (CH3).
´
the Servicio de Microanalisis of Universidad Complutense
de Madrid.
4.2.6. Isopentyl N-benzoylthiocarbamate de 3f. 76%
Yield; mp 77–78 8C; nmax/cmK1 3263 (NH), 3059 (CH),
2958 (CH), 1700 (C]O), 1601 (C]C), 1300 (C]S), 1456
(CH3); dH (CDCl3, 250 MHz), 9.22 (br s, 1H), 7.90–7.35 (m,
5H), 4.60 (t, JZ6.2 Hz, 2H), 2.00–1.60 (m, 3H), 0.95 (d,
JZ6.4 Hz, 6H); dC (CDCl3, 62 MHz), 189.7 (CS), 162.7
(CO), 133.1 (C8), 133.0 (C5), 129.0 (C6 and C10), 127.8
(C7 and C9), 72.3 (OCH2), 36.8 (OCH2CH2), 24.9 (CH),
22.4 (CH3); MS (EI): m/z (%), 251 (2), 181 (14), 121 (9),
105 (100), 77 (63), 51 (14); elemental analysis calcd (%) for
C13H17NO2S: C, 62.12; H, 6.82; N, 5.57. Found: C, 62.19;
H, 6.88; N, 5.43.
4.2. Synthesis of acylthiocarbamates 3
The corresponding acyl chlorides (0.02 mol) were dissolved
in dry acetone. To that solution, 0.02 mol of thiocyanate in
acetone was added slowly. The mixture was stirred until a
precipitate of ammonium chloride appeared. The precipitate
indicated the formation of the corresponding organic
isothiocyanate. So, to 0.02 mol of the generated isothio-
cyanate was slowly added the corresponding alcohol
dissolved in acetone. The mixture was stirred for between

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A. M. Plutın et al. / Tetrahedron 61 (2005) 5812–5817
5816
4.2.7. Octadecyl N-benzoylthiocarbamate 3g. 72% Yield;
mp 68–69 8C; nmax/cmK1 3256 (NH), 3021 (CH), 2951
(CH), 1704 (C]O), 1604 (C]C), 1300 (N–C]S); dH
(CDCl3, 250 MHz), 9.18 (br s, 1H), 7.90–7.41 (m, 5H),
4.60–4.55 (m, 2H), 1.80–1.75 (m, 2H), 1.55–1.0 (m, 30H),
0.90–0.85 (m, 3H); dC (CDCl3, 62 MHz), 189.7 (CS), 162.7
(CO), 133.1 (C5 and C8), 129.0 (C6 and C10), 127.7
(C7 and C9), 73.8 (OCH2), 31.9 (CH2(CH2)14, 31.9
(CH2(CH2)14 22.7 [CH2(CH2)14CH2], 14.1 (CH3); elemen-
tal analysis calcd (%) for C26H43NO2S: C, 72.01; H, 9.99;
N, 3.23. Found: C, 72.19; H, 9.85; N, 3.34.
2H), 1.50 (t, JZ7.1 Hz, 3H); dC (CDCl3, 62 MHz), 188.1
(CS), 152.3 (CO), 145.7 (C2), 145.5 (C5), 117.8 (C3), 112.6
(C4), 68.7 (CH2), 13.4 (CH3); MS (EI): m/z (%), 199 (2),
171 (1), 111 (1), 95 (100), 67 (6), 54 (2); elemental analysis
calcd (%) for C8H9NO3S: C, 48.23; H, 4.55; N, 7.03. Found:
C, 48.58; H, 4.92; N, 7.30.
4.2.13. Isopropyl N-(2-furoyl)thiocarbamate 3m. 73%
Yield; mp 76–78 8C; nmax/cmK1 3415 (N–H), 3132 (]CH),
2988 (CH), 1715 (C]O), 1584 (C]C), 1298 (C]S), 1013
(C–O–C); dH (CDCl3, 250 MHz), 9.27 (br s, 1H), 7.51–7.50
(m, 1H), 7.27–7.25 (m, 1H), 6.53–6.52 (m, 1H), 5.55 (hept,
JZ6.2 Hz, 1H), 1.39 (d, JZ6.3 Hz, 6H,); dC (CDCl3,
62 MHz), 187.7 (CS), 152.3 (CO), 146.1 (C2), 145.5 (C5),
118.1 (C3), 113.3 (C4), 77.65 [CH(CH3)2], 21.3. (CH3); MS
(EI): m/z (%), 213 (6), 171 (23), 111 (40), 109 (1), 95 (100),
67(4), 55 (16); elemental analysis calcd (%) for
C9H11NO3S: C, 50.69; H, 5.20; N, 6.57. Found: C, 50.88;
H, 5.72; N, 6.69.
4.2.8. Benzyl N-benzoylthiocarbamate 3h. 81% Yield; mp
104–106 8C; nmax/cmK1: 3314 (NH), 3073 (CH), 2968
(CH), 1693 (C]O), 1601 (C]C), 1269 (C]S); dH (CDCl3,
250 MHz), 9.24 (br s, 1H), 7.83–7.25 (m, 10H), 5.62
(s, 2H); dC (CDCl3, 62 MHz), 188.9 (CS), 162.8 (CO), 137.4
(C5 and C8), 131.1 (1C), 128.3 (1C), 127.3 (1C), 127.1 (1C)
(aromatic), 129.0 (C6 and C10), 127.7 (C7 and C9), 74.2
(CH2); elemental analysis calcd (%) for C15H13NO2S: C,
66.40; H, 4.83; N, 5.16. Found: C, 66.29; H, 4.99; N, 5.27.
4.2.14. Benzyl N-(2-furoyl)thiocarbamate 3n. 78% Yield;
mp 114–116 8C; nmax/cmK1 3418 (NH), 3130 (]CH), 2990
(CH), 1718 (C]O), 1609 (C]C), 1290 (C]S), 1012
(C–O–C); dH (CDCl3, 250 MHz), 9.39 (s, 1H), 7.50–7.49
(m, 1H), 7.26–7.25 (m, 1H), 6.65–6.60 (m, 1H), 5.63 (s,
2H), 7.46–7.30 (m, 5H); dC (CDCl3, 62 MHz), 184.5 (CS),
154.7 (CO), 149.9 (C2), 142.0 (C5), 137.4 (1C), 128.3 (1C),
127.3 (1C), 127.1 (1C), (Ph), 119.7 (C3), 109.5 (C4), 71.9
(CH2); MS (EI): m/z (%), 261 (!1), 171 (2), 111 (2), 95
(100), 67 (8); elemental analysis calcd (%) for C13H11NO3S:
C, 59.76; H, 4.24; N, 5.36. Found: C, 59.88; H, 4.92;
N, 5.60.
4.2.9. Isopropyl N-(4-nitrobenzoyl)thiocarbamate 3i.
71% Yield; mp 101–103 8C; nmax/cmK1 3209 (NH), 3120
(]CH), 3060 (CH), 2976 (CH), 1698 (C]O), 1601
(C]C), 1550 (NO2), 1280 (C]S); dH (CDCl3, 250 MHz),
9.45 (br s, 1H), 8.30 (d, JZ8.1 Hz, 2H), 8.04 (d, JZ8.1 Hz,
2H), 5.65 (hept, JZ6.2 Hz, 1H), 1.40 (d, JZ6.2 Hz, 6H); dC
(CDCl3, 62 MHz), 187.7 (CS), 161.7 (CO), 150.0 (C8),
138.7 (C5), 128.9 (C6, C10), 123.8 (C7, C9), 77.9
[CH(CH3)2], 21.0 (CH3); MS (EI): m/z (%), 268 (!1),
226 (3), 166 (5), 150 (100), 122 (7); elemental analysis
calcd (%) for C11H12N2O4S: C, 49.25; H, 4.51; N, 10.44.
Found: C, 49.45; H, 4.72; N, 10.50.
4.2.15. Methyl N-[3-(2-furylacryloyl)]thiocarbamate 3o.
53% Yield; mp 117–118 8C; nmax/cmK1 3254 (NH), 3118
(]CH), 2980, (C–H), 1713 (C]O), 1626 (C]C), 1278
(C]S), 1023 (C–O–C); dH (CDCl3, 250 MHz), 11.83 (br s,
1H), 7.84 (d, JZ1.7 Hz, 1H), 7.46 (d, JZ15.4 Hz, 1H), 6.92
(d, JZ3.4 Hz, 1H), 6.69 (d, JZ15.4 Hz, 1H), 6.65 (dd, JZ
3.4, 1.7 Hz, 1H), 4.02 (s, 3H); dC (CDCl3, 62 MHz), 189.8
(CS), 162.5 (CO), 151.0 (C2), 145.4 (C5), 132.5 (C6), 116.5
(C3), 116.2 (C7), 112.7 (C4), 59.4 (CH3); elemental analysis
calcd (%) for C9H9NO3S: C, 51.17; H, 4.29; N, 6.63. Found:
C, 51.48; H, 4.12; N, 6.30.
4.2.10. Isopropyl N-(4-fluorobenzoyl)thiocarbamate 3j.
74% Yield; mp 111–112 8C; nmax/cmK1 3256 (NH), 3080
(]CH), 3100 (C–H), 2974 (C–H), 1696 (C]O), 1604
(C]C), 1287 (C]S); dH (CDCl3, 250 MHz), 9.22 (br s,
1H), 7.87 (q, JZ5.2 Hz, 2H), 7.16 (t, JZ8.1 Hz, 2H), 5.63
(hept, JZ6.1 Hz, 1H), 1.43 (d, JZ6.1 Hz, 6H); dC (CDCl3,
62 MHz), 188.6 (CS), 167.6 (CO), 167.6, 163.6 (C8), 130.7
(C5), 130.4, 129.3 (C6, C10), 116.2, 115.9 (C7, C9), 77.9
OCH, 21.2 (CH3); MS (EI): m/z (%), 241 (3), 199 (15), 139
(22), 123 (100), 95 (46), 75 (19); elemental analysis calcd
(%) for C11H12FNO2S: C, 54.76; H, 5.01; N, 5.81. Found: C,
54.88; H, 5.12; N, 5.76.
4.2.16. Ethyl N-[3-(2-furyl)acryloyl]thiocarbamate 3p.
78% Yield; mp 114–116 8C; nmax/cmK1 3250 (NH), 3030
(]CH), 2982 (CH), 1716 (C]O), 1630 (C]C), 1336
(CH3), 1275 (C]S); dH (CDCl3, 250 MHz), 11.76 (br s,
1H), 7.83 (d, JZ1.6 Hz, 1H), 7.50 (d, JZ15.4 Hz, 1H), 6.92
(d, JZ3.4 Hz, 1H), 6.68 (d, JZ15.4 Hz, 1H), 6.65 (dd, JZ
3.4, 1.6 Hz, 1H), 4.50 (q, JZ7.1 Hz, 2H), 1.31 (t, JZ
7.1 Hz, 3H); dC (CDCl3, 62 MHz), 188.7 (CS), 161.9 (CO),
150.4 (C2), 145.7 (C5), 130.1 (C6), 117.3 (C3), 116.2 (C7),
112.6 (C4), 67.1 (CH2), 13.4 (CH3); elemental analysis
calcd (%) for C10H11NO3S: C, 53.32; H, 4.92; N, 6.22.
Found: C, 53.58; H, 4.82; N, 6.32.
4.2.11. Methyl N-(2-furoyl)thiocarbamate 3k. 72% Yield;
mp 97–100 8C; nmax/cmK1 3416 (NH), 3120, (]CH), 2970
(CH), 1712 (C]O), 1581 (C]C), 1298 (C]S), 1025
(C–O–C); dH (CDCl3, 250 MHz), 9.46 (br s, 1H), 7.55–7.47
(m, 1H), 7.31–7.26 (m, 1H); 6.58–6.54 (m, 1H), 4.17 (s,
3H); dC (CDCl3, 62 MHz), 189.4 (CS), 152.3 (CO), 145.9
(C2), 145.7 (C5), 118.3 (C3), 113.3 (C4), 59.4 (CH3);
elemental analysis calcd (%) for C7H7NO3S: C, 45.40; H,
3.81; N, 7.56. Found: C, 45.88; H, 3.92; N, 7.60.
4.2.12. Ethyl N-(2-furoyl)thiocarbamate 3l. 74%; mp 98–
99 8C; nmax/cmK1 3411 (NH), 3122 (]CH), 2970 (CH);
1712 (C]O), 1583 (C]C), 1310 (C]S), 1025 (C–O–C);
dH (CDCl3, 250 MHz), 9.49 (br s, 1H), 7.54–7.53 (m, 1H),
7.31–7.27 (m, 1H), 6.58–6.55 (m, 1H), 4.60 (q, JZ7.1 Hz,
4.2.17. Isopropyl N-[3-(2-furyl)acryloyl]thiocarbamate
3q. 62% Yield; mp 70–72 8C; nmax/cmK1 3251 (NH), 3120
(]CH), 2987 (CH), 1718 (C]O), 1630 (C]C), 1280
(C]S), 1020 (C–O–C); dH (CDCl3, 250 MHz), 11.76 (br s,
1H), 7.83 (d, JZ1.6 Hz, 1H), 7.43 (d, JZ15.4 Hz, 1H), 6.92

´
A. M. Plutın et al. / Tetrahedron 61 (2005) 5812–5817
5817
2. Watcher, R. USA Patent, 901053, 1990; Chem. Abstr. 1989,
111, 128868a.
(d, JZ3.4 Hz, 1H), 6.69 (d, JZ15.4 Hz, 1H), 6.65 (dd, JZ
3.4, 1.6 Hz, 1H), 5.54 (hept, JZ6.1 Hz, 1H), 1.37 (d, JZ
6.1 Hz, 6H); dC (CDCl3, 62 MHz), 188.0 (CS), 161.9 (CO),
150.4 (C5), 145.6 (C2), 130.1 (C7), 117.4 (C6), 116.2 (C4),
112.6 (C3), 77.6 [OCH(CH3)], 21.7 (CH3); MS (EI): m/z
(%), 239 (!1), 197 (2), 137 (3), 121 (100); elemental
analysis calcd (%) for C11H13NO3S: C, 55.21; H, 5.48; N,
5.85. Found: C, 55.48; H, 5.62; N, 5.60.
3. Digenis, G. A.; Rodis, N. P. USA Patent, 5539123, 1996;
Chem. Abstr. 1996, 125, 167993n.
4. Ranise, A.; Spallarossa, A.; Schenone, S.; Bruno, O.;
Bondavalli, F.; Vargiu, L.; Marceddu, T.; Mura, M.; La
Colla, P.; Pani, A. J. Med. Chem. 2003, 46, 768.
5. Quante, J. M.; Hoke, R. A.; Mize, P. D.; Woodard, D. L.;
Willner, O. L. USA Patent, 5516902, 1996; Chem. Abstr.
1996, 125, 50759z.
Acknowledgements
6. Shigeru, M.; Shigeru, M. Eur. Patent, 2394794, 1976; Chem.
Abstr. 1976, 85, 95400x.
´
We thank Ministerio de Educacion y Ciencia (CTQ2004-
01191/BQU, Spain) for financial support. J. M. C. thanks
7. Schroeder, U.; Beyer, L.; Dietze, F.; Richter, R.; Schmidt, S.;
Hoyer, E. J. Prakt. Chem. 1995, 337, 184.
´
Carmen Fernandez-Florez for her time. Our Thanks to Euan
C. Goddard for his revision of the English.
´
8. Filleux-Blanchard, M. L.; Durand-Couturier, A. Bull. Soc.
Chim. Fr. 1972, 4710.
´ ´ ´
9. Marquez, H.; Perez, E. R.; Plutın, A. M.; Morales, M.; Loupy,
A. Tetrahedron Lett. 2000, 41, 1753.
´ ´
10. Plutın, A. M.; Marquez, H.; Ochoa, E.; Morales, M.; Sosa, M.;
References and notes
´ ´ ´ ´
Moran, L.; Rodrıguez, Y.; Suarez, M.; Martın, N.; Seoane, C.
Tetrahedron 2000, 56, 1533.
11. Furyl substituent was assumed in the same orientation as that
found in the crystal and determinated by X-ray diffraction.
1. Trivedi, B. K. USA Patent, 8810816, 1988; Chem. Abstr. 1988,
108, 167428d.